Differential effects of α-catenin on the invasion and radiochemosensitivity of human colorectal cancer cells

摘要

Driven by genetic and epigenetic alterations, progression, therapy resistance and metastasis are frequent events in colorectal cancer (CRC). Although often speculated, the function of cell-cell contact for radiochemosensitivity, particularly associated with E-cadherin/catenin complex, warrants further clarification. In this study, we investigated the role of the E-cadherin/catenin complex proteins under more physiological three-dimensional (3D) cell culture conditions in a panel of CRC cell lines. In contrast to floating spheroids and growth in the laminin-rich matrix, collagen type 1 induced the formation of two distinct growth phenotypes, i.e., cell groups and single cells, in 5 out of the 8 CRC cell lines. Further characterization of these subpopulations revealed that, intriguingly, cell-cell contact proteins are important for invasion, but negligible for radiochemosensitivity, proliferation and adhesion. Despite the generation of genomic and transcriptomic data, we were unable to elucidate the mechanisms through which α-catenin affects collagen type 1 invasion. In a retrospective analysis of patients with rectal carcinoma, a low α-catenin expression trended with overall survival, as well as locoregional and distant control. Our results suggest that the E-cadherin/catenin complex proteins forming cell-cell contacts are mainly involved in the invasion, rather than the radiochemosensitivity of 3D grown CRC cells. Further studies are warranted in order to provide a better understanding of the molecular mechanisms controlling cell-cell adhesion in the context of radiochemoresistance.